An intriguing example of a differentially expressed gene is the transcription factor ETS2 , which is upregulated in chimpanzee brains relative to humans. Subtle upregulation of the orthologous Ets2 gene in developing mice can lead to cranial and cervical skeletal abnormalities reminiscent of those found in people with Down syndrome [ 11 ], but the implications of this finding to human and chimpanzee evolution are unclear. Interestingly, Watanabe et al.
They found that orthologous genes with high divergence in their 5' untranslated regions UTRs tend to show differences in expression levels. Similarly, orthologous genes associated with more diverged CpG islands also tend to show different expression levels. These two trends may be related, as CpG islands often overlap with the first exons of genes.
It has been proposed that 5' UTRs might be under positive selection in humans, possibly because of their involvement in the regulation of expression levels [ 12 ].
In related work, Enard et al. If these differences extend to the germline, they might also explain the correlation between expression and sequence divergence. But do differences in expression levels of human and chimpanzee genes necessarily have functional consequences?
The recent important paper by Khaitovich et al. Their work shows that gene-expression differences between mammalian species accumulate linearly with time, and that the rate of accumulation does not differ between intact genes and expressed pseudogenes [ 14 ]. The implication is that the majority of expression differences observed between two species, like the majority of amino-acid differences, are likely to be selectively neutral or nearly neutral and therefore of little or no functional significance.
Thus, the interpretation of species-specific expression differences will need to be based on comparisons with a null model of how expression changes under neutral evolution.
The popular media did not quite know what to make of the initial analysis of PTR22 [ 1 ]. We can now count the exact number of genetic differences between humans and chimpanzees, but whether this number is high or low is entirely in the eye of the beholder. Humans and chimpanzees are an order of magnitude more different, in terms of genetic changes, than any two humans, but an order of magnitude less different than mice and rats are from each other.
And although rat biologists will no doubt disagree, most of us might like to think that what separates us from the chimpanzee is far more profound than what separates a small rodent from a slightly larger rodent.
The major question that is before us now is thus not whether we are as different from other species as we might like to think, but rather which of the human-specific genetic changes account for our unique biological traits and which are simply evolutionary noise. Answering this question will require additional data from other primates as well as fundamental advances in our understanding of the functional evolution of both coding and non-coding sequences.
Defining what makes humans human can be tricky as more is learned about the behavior of other animals and fossils are uncovered that revise the evolutionary timeline, but scientists have discovered certain biochemical markers that are specific to humans. One factor that may account for human language acquisition and rapid cultural development is a gene mutation that only humans have on the FOXP2 gene , a gene we share with Neanderthals and chimpanzees, that is critical for the development of normal speech and language.
A study by Dr. Ajit Varki of the University of California, San Diego, found another mutation unique to humans in the polysaccharide covering of the human cell surface. Varki found that the addition of just one oxygen molecule in the polysaccharide that covers the cell surface differentiates humans from all other animals. Humans are both unique and paradoxical. While they are the most advanced species intellectually, technologically, and emotionally—extending human lifespans, creating artificial intelligence, traveling to outer space, showing great acts of heroism, altruism and compassion—they also have the capacity to engage in primitive, violent, cruel, and self-destructive behavior.
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Select basic ads. Create a personalised ads profile. Select personalised ads. Apply market research to generate audience insights. Measure content performance. Develop and improve products. List of Partners vendors. Share Flipboard Email. Lisa Marder. Lisa Marder is an artist and educator who studied drawing and painting at Harvard University.
She is an instructor at the South Shore Art Center in Massachusetts when she is not working on her own art. Featured Video. Cite this Article Format. Marder, Lisa. With my mentor David Haussler leaning over my shoulder, I looked at the top hit, a stretch of bases that together became known as human accelerated region 1 HAR1.
Using the U. Santa Cruz genome browser, a visualization tool that annotates the human genome with information from public databases, I zoomed in on HAR1. The browser showed the HAR1 sequences of a human, chimp, mouse, rat and chicken—all of the vertebrate species whose genomes had been decoded by then. It also revealed that previous large-scale screening experiments had detected HAR1 activity in two samples of human brain cells, although no scientist had named or studied the sequence yet.
We had hit the jackpot. The human brain is well known to differ considerably from the chimpanzee brain in terms of size, organization and complexity, among other traits. Yet the developmental and evolutionary mechanisms underlying the characteristics that set the human brain apart are poorly understood.
HAR1 had the potential to illuminate this most mysterious aspect of human biology. We spent the next year finding out all we could about the evolutionary history of HAR1 by comparing this region of the genome in various species, including 12 more vertebrates that were sequenced during that time.
It turns out that until humans came along, HAR1 evolved extremely slowly. In chickens and chimps—whose lineages diverged some million years ago—only two of the bases differ, compared with 18 differences between humans and chimps, whose lineages diverged far more recently. The fact that HAR1 was essentially frozen in time through hundreds of millions of years indicates that it does something very important; that it then underwent abrupt revision in humans suggests that this function was significantly modified in our lineage.
When typical genes are switched on in a cell, the cell first makes a mobile messenger RNA copy and then uses the RNA as a template for synthesizing some needed protein. The labeling revealed that HAR1 is active in a type of neuron that plays a key role in the pattern and layout of the developing cerebral cortex, the wrinkled outermost brain layer.
Malfunctions in these same neurons are also linked to the onset of schizophrenia in adulthood. HAR1 is thus active at the right time and place to be instrumental in the formation of a healthy cortex.
Other evidence suggests that it may additionally play a role in sperm production. But exactly how this piece of the genetic code affects cortex development is a mystery my colleagues and I are still trying to solve. We are eager to do so: HAR1's recent burst of substitutions may have altered our brains significantly. Beyond having a remarkable evolutionary history, HAR1 is special because it does not encode a protein.
For decades, molecular biology research focused almost exclusively on genes that specify proteins, the basic building blocks of cells. But thanks to the Human Genome Project, which sequenced our own genome, scientists now know that protein-coding genes make up just 1. The other Santa Cruz, subsequently confirmed in through lab experiments. In fact, it turns out that human HAR1 resides in two overlapping genes.
These six major groups encompass more than 1, different families of RNA genes, each one distinguished by the structure and function of the encoded RNA in the cell. HAR1 is also the first documented example of an RNA-encoding sequence that appears to have undergone positive selection.
It might seem surprising that no one paid attention to these amazing bases of the human genome earlier. But in the absence of technology for readily comparing whole genomes, researchers had no way of knowing that HAR1 was more than just another piece of junk DNA. Whole-genome comparisons in other species have also provided another crucial insight into why humans and chimps can be so different despite being much alike in their genomes.
In the past decade the genomes of thousands of species mostly microbes have been sequenced. It turns out that where DNA substitutions occur in the genome—rather than how many changes arise overall—can matter a great deal. In other words, you do not need to change very much of the genome to make a new species.
According to the researchers, when lots of enhancers target the same gene, they undergo evolutionary changes as a unit. This helps cells protect themselves from mutations in individual enhancers and ensures that important genes are transcribed at constant levels, regardless of these mutations. The redundancy of the enhancers also frees them up to change and acquire new functions so that species can rapidly adapt to new situations.
The researchers are working to perfect this technique to allow them to analyze difficult samples, such as primary tumors. Danko also plans to investigate how enhancers interact with each other by folding DNA inside the cell.
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